Like obesity, NAFLD and NASH are closely linked to nutrition and the "Western diet" which is rich in saturated fats and refined sugars. Although fat consumption has remained relatively stable, the marked increase in dietary fructose consumption (more than doubling in the past 30 years alone) supports the role of fructose in NAFLD and the metabolic syndrome. Although the mechanism(s) for fructose-related liver injury is not yet well defined, fructose-related hepatic adenosine triphosphate (ATP) depletion may contribute to liver injury. Observations in animals suggest that fructose induces metabolic syndrome and NAFLD independent of energy intake. One key difference in fructose metabolism (as opposed to glucose) relates to ATP depletion and the necessity of adenosine monophosphate (AMP) kinase to replenish ATP stores. As opposed to glucose, initial fructose metabolism involves phosphorylation of fructose to fructose-1-phosphate by fructokinase (ketohexokinase, KHK) using the substrate ATP. Unlike glucokinase, the phosphorylation of fructose by KHK is specific for fructose and not rate limited. Replenishment of ATP stores requires phosphorylation of AMP back to ATP via AMP kinase (which is inhibited in insulin resistance (common in patients with NAFLD) or conversion to uric acid via xanthine dehydrogenase resulting in hyperuricemia. The high activity of KHK in phosphorylating fructose to fructose-1-phosphate in the liver, could result in hepatic ATP depletion with habitual fructose consumption.